He studied at the Catholic College of Juilly, and then served with the French Navy before going to the United States. On Christmas Eve, 24 December 1803, nineteen-year-old Jérôme married Elizabeth ("Betsy") Patterson (1785–1879), eighteen-year-old daughter of prosperous ship-owner and merchant William Patterson, (1752–1835) in Baltimore, (then the third-largest city in America). Napoleon was unable to convince Pope Pius VII in Rome to annul their marriage, and so annulled the marriage himself (by a French imperial decree, 11 March 1805), as a matter of state. Elizabeth was pregnant with a son at the time, (Jérôme Napoléon Bonaparte (1805–1870)), and was on her way to Europe with the elder Jérôme. When they landed in neutral Portugal, Jérôme set off overland to Italy to attempt to convince his brother to recognize the marriage. Elizabeth then attempted to land in Amsterdam, hoping to travel to within the borders of France in order for her and Jerome's baby son to be born on French soil, but Emperor Napoleon I issued orders barring the ship from entering the harbour. Being with child, Elizabeth went on to England where Jérôme Napoléon Bonaparte, (later nicknamed in childhood as "Bo"), was born at 95 Camberwell Grove, Camberwell, London, England. Emperor Napoleon instituted Roman Catholic and later French state divorce proceedings only after the birth of the baby, Jerome II. After considerable delay and internal struggle, Elizabeth was later declared divorced from Jerome by a special decree and act of the state legislature of the General Assembly of Maryland in 1815.

Napoleon made his brother King of Westphalia, the short-lived realm (1807–13), created, by Napoleon, from the several states and principalities in northwestern Germany (in the former thousand-year old Holy Roman Empire). It was later reorganized by Napoleon into the Confederation of the Rhine and then after his defeat, the Allies were to reorganise the German states into a German Confederation with Austrian leadership, largely overriding prior claim of lesser states.

When Jérôme and Catharina arrived in Kassel, they found the palaces in a plundered state. As such, they placed orders for an array of stately furniture and expensive silverware with leading Parisian manufactures. Local artisans, eager for commissions, oriented themselves with these French models. The King also intended to refurbish his capital architecturally. The court theatre ranks among the small number of projects realised. Jérôme had it designed by Leo von Klenze and constructed next to the summer residence, previously known as "Wilhelmshöhe", it was changed to "Napoleonshöhe". To emphasize his rank as a ruler, and pander to his own ego, Jérôme commissioned grandiose state portraits of himself and his spouse, Queen Catharina. Other paintings were to celebrate his military exploits, with many of France's most prominent painters taken into his employ.

As a model state, the Kingdom of Westphalia was expected by Napoleon to serve as an example for the other German states. It received the first constitution and parliament to be found on German soil (decades before other parliaments, legislatures, reichstags, bundesrats, etc. such as in Frankfurt in 1848). Jérôme imported the Empire style from Paris, bestowing the new state with a modern, representative appearance. The small kingdom thus received more attention since the famous "Treaty of Westphalia" which ended the Thirty Years' War a hundred and fifty years earlier in 1648. Thanks to these efforts by King Jerome, Kassel celebrated an enormous cultural upturn.

However, Jérôme's expensive habits earned him the contempt of Napoleon. His court incurred expenses comparable to Napoleon's court (which oversaw a vastly larger and more important realm), and Napoleon refused to support Jérôme financially.[3]

In 1812, Jérôme was given command of a corps in the "Grande Armée", marching towards Minsk. Insisting on travelling "in state", Napoleon reprimanded Jerome, ordering him to leave his court and luxurious trappings behind. After the Battle of Mir (1812) Jérome occupied Mir Castle. In pique, of Napoleon's order, Jérôme returned with his entire court and train to Westphalia. After the defeat in Russia, the following winter, Jerome petitioned Napoleon to allow his wife to come to Paris, fearing the advance of the Allied armies. On the second attempt, Napoleon granted permission.

Jérôme briefly re-entered the army in 1813, when his Kingdom was being threatened from the east by the advancing allied Prussian and Russian armies. He led a small force to challenge their invasion. Following a clash with an enemy detachment, he made camp with his army, hoping for reinforcements from the French army in the west. However, before reinforcements arrived the main allied force captured the capital Kassel. The Kingdom of Westphalia was declared dissolved and Jérôme's kingship ended. He then fled to join his wife, the former queen, in France.

During the "Hundred Days", Napoleon placed Jérôme in command of the 6th Division of the II Corps under General Honoré Charles Reille. At Waterloo, Jérôme's division was to make an initial attack on Hougoumont. It is said that Napoleon wished to draw in Lord Wellington's reserves. Whatever the intent, Jérôme was allowed to enlarge the assault such that his division became completely engaged attempting to take Hougoumont to the exclusion of any other possible deployment, without significantly weakening Wellington's centre.

After the dissolution of his Kingdom, Jérôme was given the title of "Prince of Montfort" (French: prince de Montfort)[4] by his father-in-law, King Frederick I of Württemberg, in July 1816.[5] Previously, in 1814, the King had forced Jérôme and his wife to leave the country. During their exile, they visited the United States (his second time). Jérôme later returned to France and joined Napoleon during attempt to restore the Empire during the "Hundred Days".

Later, Jérôme moved to Italy, where he married his third wife, Giustina Pecori-Suárez. She was the widow of an Italian Marquess, Luigi Bartolini-Baldelli.

In 1848, his nephew, Prince Louis Napoleon, became President of the second French Republic. Jérôme was made governor of Les Invalides in Paris, which was the burial place of Napoleon I. When Louis Napoleon became emperor as Napoleon III, Jérôme was recognized as the heir presumptive to the re-established imperial throne until the birth of Napoléon Eugène, Prince Imperial. Jérôme was named a Marshal of France in 1850, served as President of the Senate (the upper house in the French Republic's parliament, compared with the lower house of the National Assembly) in 1852, and received the title of "Prince Français".

Jérôme Bonaparte died on 24 June 1860, at Villegenis, France (today known as Massy in Essonne). He is buried in Les Invalides.

Among Jérôme Bonaparte's illegitimate children was Baroness Jenny von Gustedt, born as Jeromée Catharina Rabe von Pappenheim (1811–1890). She became the grandmother of the German Socialist and Feminist writer Lily Braun.

In the Hornblower television series, he was portrayed by British actor David Birkin. The last episode (Duty) introduces Jérôme and Elizabeth ('Betsy'). Adrift in an open boat, they are picked up by Captain Hornblower's ship; Jérôme poses as a harmless Swiss citizen, but Hornblower identifies him. After many diplomatic manoeuvres, the British government decides that Jérôme is of no political importance after all, and he is allowed to return to France while Elizabeth put aboard a passing American ship.

Jerome and Betsy's marriage is portrayed in the historical novel "The Ambitious Madame Bonaparte" by Ruth Hull Chatlien, published in 2013.

Jérôme may have been a source of inspiration for the character of Prince Hans, the primary antagonist of Disney's 2013 movie musical Frozen.[citation needed]

In the 1936 musical film "Hearts Divided" Jerome was portrayed by American actor Dick Powell. Elizabeth Patterson was played by Marion Davies, with Claude Rains as Napoleon.